Smith was in his third season at the helm of the Buccaneers' defense. The 59-year-old Smith will be replaced by Mark Duffner, who served as the team's linebackers coach.
The Buccaneers have been gouged for 34.6 points per game and 355.6 passing yards, with both totals serving as the worst in the NFL. They have also surrendered 439.8 yards per contest, which ranks just above the Kansas City Chiefs for 31st in the league.
"I have the utmost respect for Mike Smith as a man and as a football coach," Buccaneers head coach Dirk Koetter said. "These decisions are always difficult, but our top priority here is to ensure that we do everything possible to help this team succeed.
"As I have said in the past, the issues we have had as a team are never one person's fault. During good times, as well as the bad, it is a collective effort between the coaches and the players. We all understand that this is a result-based profession and our results to this point have not met our standards.
"I want to thank Mike for all the hard work and passion he has displayed here on a daily basis and I wish him well moving forward."
Tampa Bay dropped its third straight decision in a 34-29 loss to the Atlanta Falcons on Sunday.
Duffner is in his third season with the Buccaneers and 22nd in the league. He has also been on the coaching staffs of the Miami Dolphins (2014-15), Jacksonville Jaguars (2006-13), Green Bay Packers (2003-05) and Cincinnati Bengals (1997-2002), where he served as defensive coordinator during his final two years.